In one study, patients treated with various doses of the human monoclonal antibody brodalumab for 12 weeks had improvements in psoriasis scores ranging from 45% to 86.3% compared with 16% for those receiving placebo (P<0.001), according to Kim A. Papp, MD, PhD, of Probity Medical Research in Waterloo, Ontario, and colleagues.

And in the second study, a reduction of 75% in psoriasis scores was seen in 77% to 83% of patients receiving higher doses of the humanized IgG4 monoclonal antibody ixekizumab compared with 8% of the placebo group (P<0.001 for all), reported Craig Leonardi, MD, of St. Louis University in St. Louis, and colleagues.

Action Points

Explain that a randomized phase II trial of brodalumab, a human anti-interleukin-17-receptor A antibody, was significantly more effective at controlling chronic plaque psoriasis at 12 weeks than placebo.

Point out that a second phase II trial found that ixekizumab, an IgG4 monoclonal antibody directed at interleukin-17, also reduced skin involvement significantly at 12 weeks compared with placebo.

Moreover, response to treatment was apparent by the end of the second week of treatment.

In an editorial accompanying the studies, Ari Waisman, PhD, of the Johannes-Gutenberg University of Mainz in Germany, pointed out that biologic therapies have greatly improved the treatment of psoriasis but can have drawbacks such as risks for severe infections, and that more targeted therapies could provide further benefit.

"Treatment with antibodies targeting interleukin-17 or its receptor should be more specific and may be expected to result in fewer side effects and therefore holds promise for patients with psoriasis," Waisman wrote.

The studies and editorial were published in the March 29 issue of the New England Journal of Medicine.

Recent investigations have implicated the family of IL-17 of cytokines in the inflammatory process of psoriasis, and a phase I study suggested efficacy after a single dose of brodalumab, a human anti-IL-17RA monoclonal antibody.

To further explore this target and identify suitable doses, Papp and colleagues enrolled 198 patients whose mean age was 43 and whose psoriasis had persisted for a mean of 19 years.

At baseline, the mean psoriasis area and severity index (PASI) score was 19 out of a total of 72, and the percentage of affected body surface was 24%.

Almost all had used topical treatments. More than two-thirds had previously been given systemic therapies and more than one-third had already had a biologic treatment.

They were randomized to receive subcutaneous brodalumab in doses of 70 mg, 140 mg, or 210 mg on day 1 and then at weeks 1, 2, 4, 6, 8, and 10, or in doses of 280 mg on day 1 and again after 1 and 2 months.

Two patients developed grade 3 neutropenia, one being considered serious.

"The exact mechanism for neutropenia is not known; however, in animal models, interleukin-17 is involved in neutrophil homeostasis through granulocyte colony-stimulating factor," the researchers observed.

In the second trial, 142 patients with moderate-to-severe plaque psoriasis were randomized to receive subcutaneous ixekizumab in doses of 10 mg, 25 mg, 75 mg, or 150 mg or placebo at baseline and week 2, and then again at months 1, 2, 3, and 4. In contrast to brodalumab, ixekizumab targets interleukin-17 directly rather than one of its receptors.

Average age was 46, and disease duration was about 16 years.

Baseline PASI scores were approximately 18.

By week 12, 90% reductions in PASI scores were seen in 50% of those receiving 25 mg of ixekizumab, and in 59% and 71% of those on 75 mg and 150 mg of the drug (P<0.001 for each compared with placebo).

Moreover, complete skin clearance was seen in 38% and 39% of the two higher dose groups (P≤0.001 versus placebo).

Physician global ratings of 0 (clear) or 1 (minimal disease) were reported for 70% to 72% in the three higher dose groups (P≤0.001 versus placebo).

Patients in those three dose groups also reported significantly better quality of life than did those on placebo.

Areas such as the scalp and nails that typically are particularly resistant to treatment also improved significantly, according to the investigators.

No serious adverse events occurred during this trial, and there were no cases of significant changes in absolute neutrophil count, anaphylaxis, serious infections, or cardiovascular events.

One patient with a history of basal cell carcinoma had two new lesions.

Editorialist Waisman noted that in both studies, the treatment seemed safe in that adverse events were minimal and few patients discontinued treatment (10 and 13 in the brodalumab and ixekizumab groups, respectively).

Nevertheless, he pointed out, 12 weeks is not a sufficient length of time to fully assess treatment safety.

"Future trials involving larger numbers of patients treated and followed for a much longer period of time will be needed," he stated.

The brodalumab study was funded by Amgen.

The lead author and co-authors disclosed received consulting fees and grant support from Amgen, as well as from multiple other companies including Abbott, Centocor, Eli Lilly, Galderma, Johnson & Johnson, Merck, Novartis, Pfizer, and GlaxoSmithKline. Five of the investigators are employees of Amgen.

The ixekizumab study was supported by Eli Lilly.

The lead author reported being a consultant and receiving investigator fees from numerous companies, including Eli Lilly, Amgen, Abbott, Centocor, Pfizer, Novartis, Novo Nordisk, and Wyeth.

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.